2-199919515-A-G

Variant names:

• chr2-199919515-A-G
• rs281787
• NM_153689.6:c.334-5547A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153689.6(C2orf69):​c.334-5547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,048 control chromosomes in the GnomAD database, including 35,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35845 hom., cov: 31)
• Consequence: C2orf69 NM_153689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 11 publications found

Genes affected

C2orf69 (HGNC:26799): (chromosome 2 open reading frame 69) Involved in oxidative phosphorylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

C2orf69 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 53

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153689.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2orf69	NM_153689.6	MANE Select	c.334-5547A>G		intron	N/A	NP_710156.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2orf69	ENST00000319974.6	TSL:1 MANE Select	c.334-5547A>G		intron	N/A	ENSP00000312770.5
	C2orf69	ENST00000491721.1	TSL:2	n.466+7744A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103803 AN: 151930 Hom.: 35791 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.683 AC: 103917 AN: 152048 Hom.: 35845 Cov.: 31 AF XY: 0.689 AC XY: 51225 AN XY: 74312

African (AFR) AF: 0.722 AC: 29965 AN: 41482

American (AMR) AF: 0.750 AC: 11461 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4078 AN: 5138

South Asian (SAS) AF: 0.829 AC: 3994 AN: 4816

European-Finnish (FIN) AF: 0.619 AC: 6536 AN: 10566

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.640 AC: 43509 AN: 67974

Other (OTH) AF: 0.658 AC: 1390 AN: 2112

Alfa AF: 0.658 Hom.: 106689

Bravo AF: 0.687

Asia WGS AF: 0.811 AC: 2822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.73
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs281787; hg19: chr2-200784238;